Pediatric Blood & Cancer最新文献

Background: While Wilms tumor (WT) typically has a favorable prognosis, relapsed cases-especially those with high-risk histology-remain therapeutically challenging after intensive frontline therapy. The combination of vincristine and irinotecan has demonstrated activity in pediatric solid tumors, and pazopanib, a multi-targeted tyrosine kinase inhibitor, might enhance treatment efficacy through antiangiogenic mechanisms.

Methods: This report included six children with relapsed WT treated between 2015 and 2022 at Bambino Gesù Children's Hospital, Rome. All patients had received prior multimodal therapy, including six chemotherapeutic agents. The VIPaz regimen (vincristine, irinotecan, pazopanib) was administered as second- or third-line therapy in combination with surgery and/or radiotherapy. Treatment response and toxicity were evaluated.

Results: Five out of six patients (83%) responded to the treatment. Three (50%) achieved complete remission and remained disease-free at 27, 74, and 76 months post-treatment. VIPaz was generally well-tolerated. No Grade >3 toxicities were observed.

Conclusion: VIPaz in combination with surgery and/or radiotherapy demonstrated an acceptable safety profile and durable responses in 50% of heavily pretreated patients with relapsed high-risk WT. Although limited by small sample size and retrospective design, these findings support further prospective evaluation of pazopanib-based regimens and biomarker-driven approaches in this population.

Background: Pediatric meningiomas make up 2% of all pediatric central nervous system tumors and are distinct from adult meningiomas, often coinciding with neurofibromatosis-2 (NF2). However, there is limited useful outcome data regarding pediatric meningiomas treated with radiation therapy (RT).

Procedures: We identified 18 pediatric patients with meningiomas treated at our institution between 2006 and 2024 with proton therapy (PT). All patients received a total dose of 50.4-59.4 Gy in 1.8 Gy/fraction daily, based on tumor grade. Nine patients had WHO Grade I meningiomas and nine had WHO Grade II meningiomas. Sixteen of 18 patients had gross disease at the time of RT. The male-to-female ratio was 1:1. Seven of 18 patients had an NF2 diagnosis. Kaplan-Meier statistical analysis was employed to estimate progression-free survival (PFS), local recurrence, and overall survival (OS) rates. We assessed toxicity during on-treatment visits and follow-ups based on severity and need for intervention.

Results: Median follow-up was 8.5 years (range: 0.5-18 years). No patients were lost to follow-up. At 10 years, local control was 87%, PFS was 75%, and OS was 94%. One patient died from a radiation-associated second neoplasm, and one died from cerebral vasculopathy occurring in the high-dose region. Other notable radiation-related toxicities included hearing loss (n = 1), cataract formation (n = 1), and endocrinopathy (n = 2). No patients had progressive vision loss.

Conclusion: This study contributes to the limited data for children with meningioma requiring RT. Long-Term disease control was encouraging and aligned with adult meningioma data. Despite the use of PT, serious radiation toxicity was observed.

Introduction: Sickle cell disease (SCD) and asthma share a complex relationship. Although estimates vary, asthma prevalence in children with SCD is believed to be comparable to or higher than the general population. Determining whether SCD confers an increased risk for asthma remains challenging due to overlapping symptoms and the multifactorial nature of asthma. This study seeks to clarify the association by assessing asthma risk in children with SCD in comparison to their siblings, controlling for potential confounders.

Methods: A prospective, case-control sibling comparison study was conducted. Children with SCD aged 2-18 years seen at our outpatient comprehensive center, along with their non-SCD siblings, were determined for diagnosed with asthma through clinical assessment by a pediatric pulmonologist.

Results: A total of 576 participants (248 SCD, 328 siblings) were included. Asthma prevalence was significantly higher in the SCD group (28.6% vs. 7.6%, p < 0.001) compared to siblings. In multivariate conditional logistic regression analysis, SCD status was the only factor associated with higher odds of asthma compared to their respective siblings, after adjusting for age and sex (odds ratio [OR]: 7.57, 95% confidence interval [CI]: 3.47-16.54, p < 0.0001). Multivariate logistic regression in the SCD group identified advancing age (OR: 1.19, 95% CI: 1.11-1.27, p < 0.001), males (OR: 2.0, 95% CI: 1.05-3.9, p = 0.04), family history of asthma (OR: 5.79, 95% CI: 2.68-12.51, p < 0.001), and hydroxyurea usage (OR: 2.11, 95% CI: 1.1-4, p = 0.02) as risk factors for asthma. Whereas males (OR: 3.32, 95% CI: 1.21-9.13, p = 0.02) and family history of asthma (OR: 2.43, 95% CI: 1.01-5.86, p = 0.048) remained risk factors for the siblings group. The inferences did not change even when age was restricted to 2-18 years in the sibling group.

Conclusion: SCD increases the risk for asthma, independent of familial and environmental factors. Age-related rise in prevalence highlights the importance of regular screening in this high-risk population.

Background: An activating NRAS p.Q61R (NRAS^Q61R) somatic mutation occurs in the lesions of patients with kaposiform lymphangiomatosis (KLA). Therapies for KLA patients are limited and since the mitogen-activated protein kinase pathway is hyperactivated by NRAS^Q61R, we evaluated the potency of Mitogen-activated protein kinase kinase (MEK) inhibitors (trametinib, selumetinib, and cobimetinib) on human NRAS^Q61R endothelial cells (ECs). RNA sequencing analysis was performed to identify dysregulated genes and those restored by trametinib. Trametinib was tested in a mouse xenograft model of NRAS^Q61R ECs.

Procedure: Doxycycline (Dox)-inducible NRAS^Q61R ECs were treated with trametinib, selumetinib, cobimetinib, or vehicle (control). Cell signaling pathways, proliferation, migration, morphology, and angiopoietin-2 (ANG-2) levels were assessed. RNA-sequencing analysis was performed on Dox-induced NRAS wild-type (NRAS^WT), NRAS^Q61R, and trametinib-treated NRAS^Q61R ECs. Selected proteins were verified by immunoblotting. NRAS^Q61R ECs were injected into nude mice on Dox-containing diet to generate xenografts and treated with trametinib or vehicle.

Results: Trametinib reduced NRAS^Q61R-activated ERK phosphorylation, cell proliferation, migration, spindling, and ANG-2 at lower doses than selumetinib or cobimetinib. RNA-sequencing detected 1315 upregulated and 1773 downregulated genes in NRAS^Q61R ECs compared with NRAS^WT. Trametinib corrected 19% upregulated and 8% downregulated genes, including elevated Notch ligands (DLL4, JAG1), activated Notch 1, and HES1. Trametinib reduced NRAS^Q61R ECs xenograft weights by 46%, vascular area by 63%, and phosphorylated ERK staining.

Conclusion: Trametinib was the most effective MEK inhibitor, correcting some dysregulated genes in NRAS^Q61R ECs, including some in the Notch pathway. Trametinib reduced vessel overgrowth in xenografts of NRAS^Q61R ECs. These studies support using trametinib treatment for KLA patients with an NRAS^Q61R mutation.

Background: Higher doses of anthracyclines and heart-relevant radiotherapy increase cardiovascular disease (CVD) risk. This study assessed CVD and CVD risk factors among adult childhood cancer survivors (CCSs) across cardiotoxic treatment risk groups and examined associations between lifestyle behaviors and treatment risks.

Methods: We invited CCSs aged ≥18 years at study, diagnosed at ages 0-20, who survived ≥5 years for an assessment of anthropometry, CVD, CVD risk factors, lifestyle, and cancer history. We classified participants into three cardiotoxic treatment risk groups (no/low risk, moderate risk, high risk) based on anthracyclines and heart-relevant radiotherapy. Multinomial logistic regression assessed lifestyle differences across groups.

Results: With a median age at study of 33 years (IQR: 26-39; 53% male), 356 CCSs participated in this study divided into the no/low risk (25%), moderate risk (40%), or high risk (35%) cardiotoxic treatment groups. Overall, CVD prevalence was 6% and similar across the three risk groups. Heart valve problems were rare, though more common in the high-risk group (no/low risk, 0%; moderate risk, 1%; vs. high risk, 4%; p = 0.037). CVD risk factors were present in 44% of CCSs-including dyslipidemia, obesity, hypertension, and diabetes-without variation across risk groups. Overall adherence to health behavior recommendations was low, with no differences in diet adherence, physical activity (PA), sedentary behavior, smoking, or alcohol consumption across cardiotoxic risk groups.

Conclusion: We found no differences in CVD, CVD risk factors, or lifestyle behaviors across cardiotoxic treatment risk groups. Health promotion that engages diet, PA, smoking cessation, and alcohol reduction should be prioritized for all CCSs regardless of cardiotoxic treatment risk levels.

Purpose: Early-Phase clinical trials in pediatric oncology are designed to test drug safety and feasibility, offering minimal direct therapeutic benefit (5%-10%) while carrying a risk of toxicity, death, and worsened symptom burden. Pediatric palliative care (PPC) provides supportive care to patients and families enrolling in Phase 1 trials; however, oncologists inconsistently refer patients for PPC. This study aimed to explore potential benefits and ideal timepoints for integrating PPC for pediatric oncology patients participating in Phase 1 trials.

Methods: Semi-Structured qualitative interviews were conducted with parents of patients enrolling in Phase 1 trials at two academic cancer centers. Interviews were audio-recorded, transcribed, and analyzed using inductive content analysis.

Results: Parents of 31 patients were interviewed. Approximately 61% of parents (n = 19) were familiar with PPC, of whom a majority (68%, n = 13) defined PPC to mean end-of-life/hospice. Fewer than one third (30%, n = 9) described the evolution of this definition to include comfort, quality of life, and extra support. Most parents (97%, n = 30) supported early integration of PPC, with 87% (n = 27) identifying enrollment on a Phase 1 study as an ideal timepoint for PPC referral. Parents described PPC as helpful with symptom management, care coordination, and general support and advocated for clinicians to introduce PPC by emphasizing these benefits.

Conclusions: Parents identified enrollment in a Phase 1 study as an ideal timepoint for PPC referral, highlighting benefits from PPC subspecialty support. Future research will assess the impact of the implementation of clinical interventions to promote PPC consultation in pediatric cancer Phase 1 trial populations.

Background: The survival outcomes among children with acute myeloid leukemia (AML) in low- and middle-income countries are still poor despite adopting modern treatment regimens from developed countries. The study aimed to identify additional potential determinant factors for relapse and death among children with AML in Thailand.

Methods: In all, data from 282 children newly diagnosed with AML between 2015 and 2019 across Thailand were retrospectively reviewed. Data, including initial white blood cell numbers, genetic analysis, post-induction minimal residual disease (MRD), hematopoietic stem cell transplantation, and supportive care, were analyzed.

Results: The probability of 5-year, event-free survival, overall survival, and cumulative incidence of relapse were 40.5%, 42.3%, and 47.4%, respectively. The risk of death was significantly increased among patients stratified as high-risk AML with an adjusted hazard ratio (HR) of 1.8 (95% confidence interval [CI]: 1.1-2.9, p = 0.01). The accessibility to MRD was significantly associated with the risk of death with an adjusted HR of 1.7 (95% CI: 1.1-2.5, p = 0.01). Patients with low-risk AML did carry a significant risk for both death, with an adjusted HR of 1.8 (95% CI: 1.1-3.0, p = 0.02), and relapse, with an adjusted HR of 2.6 (95% CI: 1.5-4.7, p < 0.001) for initial WBC greater than 100,000/mm³.

Conclusion: Elevated initial WBC numbers and accessibility to MRD could be considered additional risk factors for unfavorable outcomes in childhood AML.

Pneumocystis jirovecii pneumonia (PJP) remains a modern-day complication for pediatric patients receiving treatment for extracranial solid tumors (ST), highlighting the need for reconsideration of our current approach toward PJP prophylaxis. This critical review aims to evaluate both universal and risk-stratified approaches to PJP prophylaxis for pediatric patients with ST. It traces the evolution of prophylaxis strategies over the past six decades, with examination of trends in PJP incidence, fatality, risk factors (including those posed by novel therapeutics), prophylaxis efficacy and safety, international prophylaxis guidelines, and guideline implementation into clinical practice. Although compliant use of prophylaxis effectively prevents PJP, our understanding of specific risk factors and prophylaxis-related toxicity has predominantly been established for pediatric patients with hematological rather than ST. This complicates our assessment of the risks and benefits of PJP prophylaxis for those with ST, resulting in variations in prophylaxis guidance and practices, and is further compounded by increased use of novel immunomodulating agents. These knowledge gaps make it difficult to reliably inform a risk-stratified approach to PJP prophylaxis in pediatric patients with extracranial ST. Further longitudinal research and implementation strategies are required to support the development of effective, standardized PJP prophylaxis practices.

Introduction: The combination of disease manifestations, the familial burden, and varying penetrance of endocrine tumor syndromes (ETSs) is unique. This review aimed to portray and summarize available data on psychosocial outcomes in patients with ETSs and explore gaps and opportunities for future research and care.

Methods: Literature was systematically searched for articles on psychosocial outcomes in patients with multiple endocrine neoplasia (MEN), von Hippel-Lindau (VHL), and pathogenic variants (PVs) in succinate dehydrogenase (SDHx) genes via PubMed, PsychInfo, and Embase. Study quality was assessed using the CASP and STROBE appraisal tools.

Results: In total, 36 studies were found with fluctuating levels of evidence, of which five included pediatric patients. Overall, studies showed a considerable impact of ETSs on psychosocial outcomes such as quality of life (QoL), anxiety, and depression. Maladaptive coping, as well as social and financial restraints, were associated with poorer psychosocial outcomes. Surveillance protocols had ambivalent effects, both creating a sense of control and serving as a constant reminder of having an ETS. Parathyroid disease was associated with adverse psychosocial effects in MEN1. In MEN2A, gastrointestinal symptoms and having affected offspring were associated with poorer psychosocial outcomes. In MEN2B, pain was reported to interfere with daily life. Studies regarding VHL reported a wide range of experiences in patients and family members. Only a few studies were found for patients with PVs in SDHx genes, mainly describing effects due to the manifestation of disease or paraganglioma.

Conclusions: Psychosocial outcomes and possible underlying factors seem different for each ETS. More research is needed to address psychosocial outcomes in children with an ETS.